Karim S Shalaby1, Mahmoud E Soliman1, Giulia Bonacucina2, Marco Cespi2, Giovanni F Palmieri2, Omaima A Sammour1, Abdelhameed A El Shamy1, Lisbeth Illum3, Luca Casettari4. 1. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, 11566, Cairo, Egypt. 2. School of Pharmacy, University of Camerino, Via S. Agostino 1, 62032, Camerino, MC, Italy. 3. IDentity, 19 Cavendish Crescent North, The Park, Nottingham, NG7 1BA, UK. 4. Department of Biomolecular Sciences, School of Pharmacy, University of Urbino, Piazza Rinascimento, 6, 61029, Urbino, PU, Italy. luca.casettari@uniurb.it.
Abstract
PURPOSE: Biodegradable polymeric nanoparticles of different architectures based on polyethylene glycol-co-poly(ε-caprolactone) block copolymers have been loaded with noscapine (NOS) to study their effect on its anticancer activity. It was intended to use solubility of NOS in an acidic environment and ability of the nanoparticles to passively target drugs into cancer tissue to modify the NOS pharmacokinetic properties and reduce the requirement for frequent injections. METHODS: Linear and star-shaped copolymers were synthetized and used to formulate NOS loaded nanoparticles. Cytotoxicity was performed using a sulforhodamine B method on MCF-7 cells, while biocompatibility was determined on rats followed by hematological and histopathological investigations. RESULTS: Formulae with the smallest particle sizes and adequate entrapment efficiency revealed that NOS loaded nanoparticles showed higher extent of release at pH 4.5. Colloidal stability suggested that nanoparticles would be stable in blood when injected into the systemic circulation. Loaded nanoparticles had IC50 values lower than free drug. Hematological and histopathological studies showed no difference between treated and control groups. Pharmacokinetic analysis revealed that formulation P1 had a prolonged half-life and better bioavailability compared to drug solution. CONCLUSIONS: Formulation of NOS into biodegradable polymeric nanoparticles has increased its efficacy and residence on cancer cells while passively avoiding normal body tissues. Graphical Abstract ᅟ.
PURPOSE: Biodegradable polymeric nanoparticles of different architectures based on polyethylene glycol-co-poly(ε-caprolactone) block copolymers have been loaded with noscapine (NOS) to study their effect on its anticancer activity. It was intended to use solubility of NOS in an acidic environment and ability of the nanoparticles to passively target drugs into cancer tissue to modify the NOS pharmacokinetic properties and reduce the requirement for frequent injections. METHODS: Linear and star-shaped copolymers were synthetized and used to formulate NOS loaded nanoparticles. Cytotoxicity was performed using a sulforhodamine B method on MCF-7 cells, while biocompatibility was determined on rats followed by hematological and histopathological investigations. RESULTS: Formulae with the smallest particle sizes and adequate entrapment efficiency revealed that NOS loaded nanoparticles showed higher extent of release at pH 4.5. Colloidal stability suggested that nanoparticles would be stable in blood when injected into the systemic circulation. Loaded nanoparticles had IC50 values lower than free drug. Hematological and histopathological studies showed no difference between treated and control groups. Pharmacokinetic analysis revealed that formulation P1 had a prolonged half-life and better bioavailability compared to drug solution. CONCLUSIONS: Formulation of NOS into biodegradable polymeric nanoparticles has increased its efficacy and residence on cancer cells while passively avoiding normal body tissues. Graphical Abstract ᅟ.
Authors: Samer R Abulateefeh; Aram O Saeed; Jonathan W Aylott; Weng C Chan; Martin C Garnett; Brian R Saunders; Cameron Alexander Journal: Chem Commun (Camb) Date: 2009-08-24 Impact factor: 6.222
Authors: P Skehan; R Storeng; D Scudiero; A Monks; J McMahon; D Vistica; J T Warren; H Bokesch; S Kenney; M R Boyd Journal: J Natl Cancer Inst Date: 1990-07-04 Impact factor: 13.506